N-Terminal Pro–B-Type Natriuretic Peptide Identifies Patients With Chest Pain at High Long-Term Cardiovascular Risk

Study Questions:

Are elevated levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) predictive of long-term cardiovascular (CV) risk in patients who present with chest pain, even if they rule out for acute coronary syndrome (ACS)?


Patients presenting to an emergency department within 6 hours of onset of chest pain with a normal or nondiagnostic electrocardiogram (ECG) were evaluated for ACS (troponin T, recurrent angina, and serial ECGs). CRP and NT-proBNP levels were also measured.


A total of 524 patients were included (145 with ACS and 379 with rule-out ACS). Follow-up at 9 and 10 years occurred in 96% of the study population. Death occurred in 15% of patients: 11% from the rule-out group and 24% from the ACS group (p < 0.001). In the rule-out group, 42% of deaths were cardiovascular compared to 69% in the ACS group (p < 0.001). Age >65 years, previous myocardial infarction, known chronic heart failure, a nondiagnostic ECG on admission, and elevated NT-proBNP levels (>87 pg/ml) were independent predictors of long-term CV mortality in the rule-out group. In the ACS group, these predictors were age >65 years, documented coronary artery disease, and elevated NT-proBNP levels. Elevated CRP levels were an independent predictor for CV mortality in patients with rule-out at 3-year follow-up only. In rule-out patients with normal CRP and NT-proBNP levels, the CV mortality rate was 4.7 per 1,000 person-years, compared with a death rate of 20 in patients with both biomarkers elevated, which was comparable to the 17.9 per 1,000 person-year incidence rate in patients with ACS.


The authors concluded that a positive biomarker panel discriminates patients that rule out for ACS who have a high risk for long-term CV mortality.


Several studies have shown that certain biomarkers may be useful in stratifying patients for risk of CV complications. However, the utility of biomarker analysis in low-risk patients without manifest CV disease is controversial. This study, along with other recent studies using high-sensitive cardiac troponin T assays indicate that underlying chronic, silent, vascular processes may be detectable in populations deemed at otherwise low risk. The mechanism(s) responsible for these biomarker elevations and the potential usefulness of a therapeutic intervention aimed at reducing the elevated risk associated with the biomarker elevation will require further study.

Clinical Topics: Acute Coronary Syndromes, Heart Failure and Cardiomyopathies, Atherosclerotic Disease (CAD/PAD), ACS and Cardiac Biomarkers, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Coronary Artery Disease, Myocardial Infarction, Acute Coronary Syndrome, Follow-Up Studies, Troponin T, Risk Factors, Electrocardiography, Natriuretic Peptides, Incidence, C-Reactive Protein, Biological Markers, Outpatients, Troponin I, Chest Pain, Heart Failure, Cardiovascular Diseases

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